Hepatic sialic acid synthesis modulates glucose homeostasis in both liver and skeletal muscle.

ABSTRACT:

Objective

Sialic acid is a terminal monosaccharide of glycans in glycoproteins and glycolipids, and its derivation from glucose is regulated by the rate-limiting enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE). Although the glycans on key endogenous hepatic proteins governing glucose metabolism are sialylated, how sialic acid synthesis and sialylation in the liver influence glucose homeostasis is unknown. Studies were designed to fill this knowledge gap.

Methods

To decrease the production of sialic acid and sialylation in hepatocytes, a hepatocyte-specific GNE knockdown mouse model was generated, and systemic glucose metabolism, hepatic insulin signaling and glucagon signaling were evaluated in vivo or in primary hepatocytes. Peripheral insulin sensitivity was also assesse

SUBMITTER: Peng J 

PROVIDER: S-EPMC10583174 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature